We wish to determine the in vivo and in vitro interactions with mammalian DNA of (a) the antineoplastic drug cis-DDP and, (b) analogous ruthenium (Ru) ammine and nitrosyl compounds synthesized in this laboratory. First, using chemical and biophysical techniques, the kinds of reactions of cis-DDP and ruthenium compounds with DNA will be documented. These studies will be performed using exact molar ratios of drugs to DNA. Thus, the stoichiometry, kinetics and specificity of their reactions with DNA and chromatin will be determined. The biological studies outlined are designed to test our working hypohtesis on the increased sensitivity of new DNA and high G-C DNA to platinization. Information obtained from the platinum drug studies will be used in a program for biophysical analysis as well as for screening ruthenium compounds for potential antitumor activity.